Li Liangwei, Peng Guangda, Liu Xiaowei, Zhang Yinwei, Han Hongwei, Liu Zhi-Ren
Department of Biology, Georgia State University, 145 Piedmont Ave SE, Atlanta, GA 30303, USA.
iScience. 2020 Oct 15;23(11):101684. doi: 10.1016/j.isci.2020.101684. eCollection 2020 Nov 20.
Cancer cells alter their nutrition metabolism to cope the stressful environment. One important metabolism adjustment is that cancer cells activate glutaminolysis in response to the reduced carbon from glucose entering into the TCA cycle due to inactivation of several enzymes in glycolysis. An important question is how the cancer cells coordinate the changes of glycolysis and glutaminolysis. In this report, we demonstrate that the pyruvate kinase inactive dimer PKM2 facilitates activation of glutaminolysis. Our experiments show that growth stimulations promote PKM2 dimer. The dimer PKM2 plays a role in regulation of glutaminolysis by upregulation of mitochondrial glutaminase I (GLS-1). PKM2 dimer regulates the GLS-1 expression by controlling internal ribosome entry site (IRES)-dependent c-myc translation. Growth stimulations promote PKM2 interacting with c-myc IRES-RNA, thus facilitating c-myc IRES-dependent translation. Our study reveals an important linker that coordinates the metabolism adjustment in cancer cells.
癌细胞改变其营养代谢以应对压力环境。一种重要的代谢调节是，由于糖酵解中几种酶的失活，进入三羧酸循环的葡萄糖碳减少，癌细胞会激活谷氨酰胺分解。一个重要的问题是癌细胞如何协调糖酵解和谷氨酰胺分解的变化。在本报告中，我们证明丙酮酸激酶无活性二聚体PKM2促进谷氨酰胺分解的激活。我们的实验表明，生长刺激促进PKM2二聚体的形成。二聚体PKM2通过上调线粒体谷氨酰胺酶I（GLS-1）在谷氨酰胺分解的调节中发挥作用。PKM2二聚体通过控制内部核糖体进入位点（IRES）依赖性的c-myc翻译来调节GLS-1的表达。生长刺激促进PKM2与c-myc IRES-RNA相互作用，从而促进c-myc IRES依赖性翻译。我们的研究揭示了一个协调癌细胞代谢调节的重要连接物。
